CML, myeloproliferative disorders and bone marrow biopsy

CML, myeloproliferative disorders and bone marrow biopsy

1. Myeloproliferative disorders

   • 4 types of myeloproliferative disorders
     • Positive for Philadelphia chromosome
       • Chronic myelogenous leukemia (CML)
         • Clinical phases are differentiated according to the amount of blasts present in the blood
       • Translocation between ch 9 and 22
     • Negative for Philadelphia chromosome
       • Polycitemia vera (PV)
       • Essential thrombocytosis (ET)
       • Primary Myelofibrosis (PMF)
         • In the late phases the target is also the bone -> osteomyelosclerosis
   • The first thing to do is to reduce leukocytosis
     • Hyperhydrating the patient and giving him hydroxyurea

2. CML

   • High sensitivity to the alloreactivity of the allogenase transplant
   • Response to therapy
     • Hematologic data
     • Cytogenetics
       • With FISH you have greater number of cells to analyze because you don't need to have the cells replicating, so it is more sensitive than cytogenetics
       • qRT-PCR is even more sensitive
       • Cytogenetic response translates into a prognostic value
     • With molecular response criteria you have an earlier chance of identifying patients who have the best response to the treatment you are giving
     • Major molecular response
       • 3Log reduction in the qRT-PCR
     • Complete molecular response
       • >4.5Log reduction from the IRIS baseline

3. Primary myelofibrosis

   • Risk factors associated with PMF
     • Age >65 years
     • Constitutional symptoms
     • Circulating blasts (>1% in peripheral blood)
     • Hb <10 g/L
     • WBC > 25x10^9/L: leukocytosis
   • Prognosis after risk score calculation
     • Low risk: median survival of 135 months
     • Intermediate (1): median survival of 95 months
     • Intermediate (2): median survival of 48 months
     • High (>3): median survival of 27 months
   • Therapy
     • Transplant
     • Targeted therapy
       • Inhibitors of JAK2 mutation
         • Ruxolitinib
           • Excellent patient survival and outcome compared to historical controls
     • Other therapies
       • Erythropoietin or Danazol stimulate erythrocyte production
       • Hydroxyurea and splenectomy to reduce the burden of the extra medullary hematopoiesis
       • Prednisone can be used to reduce symptoms
         • Most of them are related to the disease-cells production of cytokines
   • Clinical features
     • Splenomegaly
     • Fever and some fibrosis in the bones
       • Cytokines that induce fibrogenesis in the bone marrow

4. Bone marrow biopsy

   • Indications
     • Staging of lymphoproliferative disorders
     • Diagnosis of some lymphoproliferative disorders
       • Only hairy cell leukemia and lymphoblastic lymphomas
     • Suspicious metastatic involvement
     • Chronic myeloproliferative disorders
     • Aplastic anemia
     • Myelodysplastic syndromes
     • Fever of unknown origin
     • Inadequate BM aspiration
     • Plasma cell dyscrasia
     • Acute leukemia
     • Amyloidosis
     • Bone disease

5. Imatinib

   • Tyrosine-kinase inhibitor
   • At 12 months from the beginning of the therapy we cannot have Philadelphia chromosome
   • Second generation TKIs
     • Nilotinib, Dasatinib, Bosutinib, Panatinib
       • Nilotinib is faster, more effective and gives you a greater chance of survival earlier in the treatment
     • They would be normally used before a bone marrow transplant
   • Resistance mechanisms to Imatinib
     • Patient compliance
     • Absorption
     • "Pure" resistance
       • New mutations of the Bcr-Abl gene
     • If patient after a year of treatment shows no progression, then the patient is a strong candidate for a BMT

6. Lymphomas

   • Diffuse large B-cell lymphoma

7. Fever of unknown origin is an indication for bone marrow biopsy

8. Myelodisplastic syndromes

   • Bone marrow aspiration is superior to biopsy